Most patients with triple-negative breast cancer should undergo genetic testing for mutations in known breast cancer predisposition genes, including BRCA1 and BRCA2, a Mayo Clinic-led study has found. The findings come from the largest analysis to date of genetic mutations in this aggressive form of breast cancer. The results of the research appear in the Journal of Clinical Oncology. "Clinicians need to think hard about screening all their triple-negative patients for mutations because there is a lot of value in learning that information, both in terms of the risk of recurrence to the individual and the risk to family members. In addition, there may be very specific therapeutic benefits of knowing if you have a mutation in a particular gene," says Fergus Couch, Ph.D., professor of laboratory medicine and pathology at Mayo Clinic and lead author of the study.

The study found that almost 15 percent of triple-negative breast cancer patients had deleterious (harmful) mutations in predisposition genes. The vast majority of these mutations appeared in genes involved in the repair of DNA damage, suggesting that the origins of triple-negative breast cancer may be different from other forms of the disease. The study also provides evidence in support of the National Comprehensive Cancer Network (NCCN) guidelines for genetic testing of triple-negative breast cancer patients.

Triple-negative breast cancer is a specific subset of breast cancer that makes up about 12 to 15 percent of all cases. The disease is difficult to treat because the tumors are missing the estrogen, progesterone and HER-2 receptors that are the target of the most common and most effective forms of therapy. However, recent studies have suggested that triple-negative breast cancer patients might harbor genetic mutations that make them more likely to respond to alternative treatments like cisplatin, a chemotherapy agent, or PARP inhibitors, anti-cancer agents that inhibit the poly (ADP-ribose) polymerase (PARP) family of enzymes.

Dr. Couch and his colleagues decided to assess the frequency of mutations in predisposition genes in patients with triple-negative breast cancer to further delineate the role of genetic screening for individuals with the disease. The researchers sequenced DNA from 1,824 triple-negative breast cancer cases seen at 12 oncology clinics in the U.S. and Europe, as part of the Triple-Negative Breast Cancer Consortium.